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Thymoquinone (TQ) is the main active ingredient of Nigella sativa seeds with various pharmacological effects. The aim of this study was to investigate the effect of TQ on renal fibrosis and permeability and oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Eighty male Wistar rats were divided into 5 groups as follow: control (received normal saline), LPS (1 mg/kg/day), and LPS+TQ (by doses of 2, 5 and 10 mg/kg/day). After three weeks, the biochemical parameters such as blood urea nitrogen (BUN) and creatinine in serum samples, oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase (CAT) activities in renal tissue homogenate and renal permeability (evaluated by Evan’s blue dye method) were measured and renal fibrosis was evaluated, histologically using Masson’s trichrome staining. LPS administration induced renal fibrosis (1.49 ± 0.08 vs. 7.15 ± 0.18%) and significantly increased renal permeability (6.03 ± 1.05 vs. 13.5 ± 1.04 μg evans blue(EB)/g tissue), serum BUN and creatinine levels and oxidative stress marker (MDA) (P < 0.05), while, it reduced anti-oxidative markers including total thiol group, SOD and CAT activities (P < 0.05). Administration of TQ significantly improved these alterations which were dose-dependent in oxidative stress markers, renal permeability (TQ 2, 5 and 10 mg/kg: 10.7 ± 0.3, 9.2 ± 1.4 and 11.5 ± 0.6 μg EB/g tissue; respectively) and fibrosis (TQ 2, 5 and 10 mg/kg: 6.09 ± 0.7, 4.26 ± 0.14 and 2.52 ± 0.08%; respectively). In conclusion, administration of TQ reduced renal fibrosis and permeability and improved oxidative stress status. Thus, TQ can be considered in conditions accompanied with chronic inflammation at least as a part of treatment strategy.

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Anti-inflammatory, antioxidant, and immunomodulatory effects of thymoquinone (TQ) have been shown. The effects of TQ on lipopolysaccharide- (LPS-) induced inflammation and pathological changes in rats’ lung were investigated in this study. Four groups of rats included (1) control (saline treated); (2) LPS (treated with 1 mg/kg/day i.p. for two weeks); and (3 and 4) 5 or 10 mg/kg TQ i.p. 30 min prior to LPS administration. Total and differential WBC counts in the blood and bronchoalveolar fluid (BALF), TGF-β1, INF-γ, PGE2, and IL-4 levels in the BALF and pathological changes of the lung were evaluated. Total WBC count and eosinophil, neutrophil, and monocyte percentage were increased, but the lymphocyte percentage was reduced in the blood and BALF. The BALF levels of PGE2, TGF-β1, and INF-γ were also increased, but IL-4 level was reduced due to LPS administration. LPS also induced pathological insults in the lung of rats ( P < 0.05 to P < 0.001 for all changes in LPS-exposed animals). Treatment with TQ showed a significant improvement in all changes induced by LPS ( P < 0.05 to P < 0.05 ). TQ showed a protective effect on LPS-induced lung inflammation and pathological changes in rats which suggested a therapeutic potential for TQ on lung injury.

Inflammation is a physiological response of immune system against internal and external harmful stimulus. However, inflammation is a double-edged sword and can be harmful if it is not properly controlled. Nowadays inflammation is considered as an important factor in the pathophysiology of neurological diseases. Neuroinflammation can be as a result of direct damage to the brain tissues or induced by systemic inflammation. This process is characterized by microglial activation, stimulates astrocytes, blood-brain barrier breakdown and consequent increase in the permeability, penetration of peripheral immune cells into parenchyma of the central nervous system, excessive production of cytokines, nitric oxide, reactive oxygen species as well as prostaglandins and finally, neuronal damage and death. In this study, neuroinflammation and its role in the pathophysiology of brain diseases, including Alzheimer›s disease, Parkinson›s disease, Huntington›s disease, depression, anxiety, epilepsy, schizophrenia and autism are outlined and discussed. Conclusion: Although inflammation has a prominent role in the pathogenesis of neurological diseases, there are no effective and safe treatments to control deregulated inflammatory processes in the brain. The medications usually used to control inflammation are not fully effective in the brain due to lack of BBB penetration. Since many inflammatory processes in the brain is beneficial, modulation of inflammatory responses will be a more efficient therapeutic approach than suppression of inflammatory processes.

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

Background: Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro-ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice. Methods: Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydroethanolic extract of TP (50, 100 and 200 mg/kg); ( 6) n-butanol (NBut) (100 mg/kg) and ( 7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion:Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Background: Brain tissues oxidative damage has been proposed to occur as a result of epileptic seizures. With respect to the antioxidant effects of Pinus eldarica (P. eldarica), the impacts of a hydroalcoholic extract of the plant on the brain tissues oxidative damage taking after seizures induced by Pentylenetetrazole (PTZ) was investigated in rats. Methods: The rats were divided into 6 groups and treated: (1) Control(saline); (2) PTZ (100 mg/kg, i.p.), [3-6] four doses including 20, 50, 200 and 500 mg/kg of P. eldarica extract (Ext 20, Ext 50, Ext 200, Ext 500) 30 min before PTZ injection. Latencies to the first Minimal Clonic (MCS) and Generalized Tonic-Clonic (GTCS) seizures were recorded. The hippocampal tissues were then collected for biochemical measurements. Results: The extract non-significantly postponed both the MCS and GTCS onsets. PTZ- induced seizure increased Malondialdehyde (MDA) (P<0.001) concentration while, diminished thiol contents (P<0.01) of hippocampal tissues. Pretreatment with 200 mg of the extract diminished MDA level in the hippocampal tissues compared to the PTZ group (P<0.001). Both 50 and 200 mg/kg of the extract improved thiol concentration in the hippocampal tissues (p<0.01). Conclusion: The present study demonstrated that the extract of P. eldarica possess protective effects against hippocampal tissues oxidative damage in PTZ- induced seizure model.